Compositions of Iron-Doped Apatite Nanoparticles (IDANP's) herein described, dramatically decrease viral infection, and are largely non-toxic. As such, IDANP's are useful for the prevention, treatment, or alleviation of signs or symptoms associated with viral activation or infection. The nanoparticles (NPs) used in this research are composed of hydroxyapatite (HA) Ca10(PO4)6(OH)2, doped with iron. HA, which is a constituent of mammalian bones and teeth, has been extensively studied and approved by the Food and Drug Administration (FDA) for applications in medicine and dentistry (Palmer et al., Chemical Reviews, 2008 & Hench, Journal of the American Ceramic Society, 1998).
In a publication by Felix d'Herelle in 1931, viruses which specifically kill bacteria were used to treat acute bacterial infection (d'Herelle, Bulletin of the New York Academy of Medicine, 1931). These viruses were termed bacteriophage (phage) by d'Herelle, and treatment of bacterial infection by phage has since been referred to as phage therapy. However, the discovery and use of traditional antibiotics such as penicillin (Fleming, British Journal of Experimental Pathology, 1929) de-emphasized wide spread use of phage therapy. In 2013, the Centers for Disease Control and Prevention estimated that each year, 2 million people in the United States become infected with antibiotic-resistant bacteria, of which, approximately 23,000 die as a direct result of such infections (2013). Rapid bacterial resistance to traditional antibiotics therefore calls for alternative therapies such as phage therapy to be revisited. Previous research has shown that addition of IDANPs to bacteria prior to phage exposure results in increased bacterial plaques in vitro (Andriolo et al., Journal of Vacuum Science and Technology B, 2013). Because IDANPs enhance phage killing of bacteria, initial interest in their study as an adjuvant to phage therapy was garnered.
Bacterial viruses (phage) and human viruses have many similarities including structure and mechanism of infection. To ensure safety of IDANPs in a human system, it had to be established that while these nanoparticles (NPs) increased phage infection and killing of bacterial cells, that IDANPs did not also increase eukaryotic virus infections and killing of eukaryotic cells. To test IDANP-effect on eukaryotic virus infection of eukaryotic cells, experiments were carried out using Chlorella variabilis NC64A (NC64A) and its virus, Paramecium bursaria chlorella virus 1 (PBCV-1) (Andriolo et al., IEEE Transactions on Nanobioscience, 2016). Results indicated that in an algal system, viral infections were not increased or decreased by the addition of IDANPs.
Previous work has shown iron(III) inactivates HSV-1 (Sagripanti et al., Applied and Environmental Microbiology, 1993), and in more recent studies, it has been shown that iron(III) inhibits replication of DNA and RNA viruses (Terpilowska et al., Biometals, 2017). However, specific therapeutic applications of IDANPs regarding viral infection have previously not been disclosed or studied. The IDANP compositions and methods of use herein described, dramatically decrease viral infection, and are largely non-toxic to mammalian cells. As such, IDANP's are useful for the prevention, treatment, or alleviation of signs or symptoms associated with viral activation or infection.